Chemistry 125 Lecture 34 December 2 2009 The

Chemistry 125: Lecture 34 December 2, 2009 The Conformation of Cycloalkanes Understanding conformational relationships makes it easy to draw idealized chair structures for cyclohexane and to visualize axial-equatorial interconversion. The conformational energy of cyclic alkanes illustrates the use of molecular mechanics, a useful, but highly empirical scheme for reckoning conformational energy. For copyright notice see final page of this file

Ernst Mohr Illustrations (1918) What o’clock? Z ? ? Drawing chair cyclohexane rings: opposite C-C bonds are parallel axial bonds are parallel to 3 -fold axis equatorial bonds are (anti)parallel to next-adjacent C-C bonds

Cholic Acid Glucose (a Steroid) (a Carbohydrate)

For such problems D. H. R. Barton Invents Conformational Analysis (1950) b “up” ; “down” Intermediates in steroid hormone synthesis Barton redraws Ring A C A (for molecule in conventional orientation, old-fashioned configuration notation, like cis / trans) D B Baeyer observed only one c-Hexyl-COOH, but in these epimers, and OH groups have different reactivity! (configurationally diastereotopic)

For such problems D. H. R. Barton Invents Conformational Analysis (1950) b “up” ; “down” ERRORS? (for molecule in conventional orientation, old-fashioned configuration notation, like cis / trans) (e) “equatorial” ) Ring Flip? (p) “polar” (now axial) 3 -fold axis Cf. ~1950 Stereochemistry: Bijvoet, Newman, CIP, (Molecular Mechanics) (Nobel Prize 1969 for “development of the concept of conformation and its application in chemistry”)

Ernst Mohr Illustrations (1918) gauche, but not anti, is OK for the second ring of decalin. anti N. B. During flip equatorials become axials and vice versa. gauche fused chairs in "decalin" (decahydronaphthalene) Try with models if you’re skeptical. Ring flip impossible for trans decalin!

Mol 4 D (CMBI Radboud University, Nijmegen, NL) Conformational Jmol Animations Click for INDEX or go to http: //cheminf. cmbi. ru. nl/wetche/organic/index. html (see Wiki to install Jmol)

Mol 4 D (CMBI Radboud University, Nijmegen, NL) Click Points Ethane Click to Animate or go to http: //cheminf. cmbi. ru. nl/wetche/organic/nalkanesconf/ethane/jmindex. html Staggered Eclipsed barrier ~5. 2 k. J/mol 0. 239 = 1. 24 kcal/mol Should be ~2. 9 kcal/mol. Caveat emptor! Step Keys

Mol 4 D (CMBI Radboud University, Nijmegen, NL) Propane Click to Animate or go to http: //cheminf. cmbi. ru. nl/wetche/organic/nalkanesconf/propane/jmproprot. html Eclipsed 3. 3 kcal/mol Staggered

Mol 4 D (CMBI Radboud University, Nijmegen, NL) Butane (central bond) Click to Animate or go to http: //cheminf. cmbi. ru. nl/wetche/organic/nalkanesconf/butane/jmindex. html Anti Gauche+ 1013 10 -3/4 3. 4 = 10 10. 5 /sec eclipsed 3. 5 kcal/mol fully eclipsed ~ 5. 5 kcal/mol? (experimentally irrelevant) (tells how fast) Anti Gauche- Gauche + 0. 9 kcal/mol (tells how much) Gauche+ / Anti = 10 -3/4 0. 9 = 10 -0. 68 = 1 / 4. 7 Gauche / Anti = 2 10 -3/4 0. 9 = 2 10 -0. 68 = 1 / 2. 4

Conformational Energy of Ethane Butane Energy (kcal/mole) 5. 5 3 3 0. 9 (0. 6? ) 0° CHCH 3 3 5. 5 120° CH 3 Torsional Angle CH 3 CH 3 H 360° 240° CH 3 CHCH 3 3

Mol 4 D (CMBI Radboud University, Nijmegen, NL) Ring Flip of c-Hexane Click to Animate or go to http: //cheminf. cmbi. ru. nl/wetche/organic/cyclohexane/jm/chxjmol. html Barrier (Half-Chair) ~ 11 kcal/mol Chair conformer Flexible or Twist-Boat conformer ~5. 5 kcal/mol

Mol 4 D (CMBI Radboud University, Nijmegen, NL) Flexible c-Hexane Click to Animate or go to http: //cheminf. cmbi. ru. nl/wetche/organic/cyclohexane/jm/twist_boat. html Barrier (Boat) ~ 1 kcal/mol Flexible or Twist-Boat Form The boat is not an isomer (an energy minimum), it is a barrier on the pleasantly smooth path between twist-boat isomers.

Shape, “Strain Energy” & Molecular Mechanics “Hooke’s Law” for Strain Energy

Molecular Mechanics (1946) Question: How did having COOH groups on the benzene rings facilitate the experiment? At the barrier the C-C-Br angles open by 12°. Activation Energy for Racemization obs. 19. 5 kcal/mol t 1/2 = 9 min at 0°C (1013 10 -(3/4)*20 ~ 10 -2/sec) calc. 17. 3 kcal/mol

“Molecular Mechanics” programs calculate (and can minimize) strain assuming that molecules can be treated as (electro)mechanical entities. To achieve useful precision they require a very large set of empirical force constants adjusted arbitrarily to make energies match experiment (or reliable quantum calculations).

“MM 2” Parameters 66 different atoms types (including 14 different types of carbon) 138 different bond stretches (41 alkane carbon-X bonds)

“MM 2” Parameters 66 different atoms types (including 14 different types of carbon) 624 different bond bendings (41 alkane-X angles)

“MM 2” Parameters 66 different atoms types (including 14 different types of carbon) Overall Butane 0. 5 just tweaked a bit by torsional energy in this scheme 180° is low “because of” low van der Waals repulsion kcal/mole 1494 different bond twistings 0 120° 240° (37 alkane-alkane-X twists)360° -0. 5 Sum: 1 -1 -1 -1 Torsional Contribution to Butane

After simplification “MM 3” has >2000 Arbitratily Adjustable Parameters ! Contrast with quantum mechanics, where there are no arbitrary parameters. (just particle masses, integral charges & Planck's constant)

Catalogue of Molecular Mechanics Schemes from Wikipedia: Force Fields (Chemistry) We’ve come a long way from Couper, Crum-Brown, and Dewar

1 e. g. gauche C-C-C-C (unfavorable) 21 43 4 5 23 e. g. favorable C…H “Ideal” Cyclohexane (by Molecular Mechanics) Strain (kcal/mol) 0. 33 Stretch 0. 00 0. 36 Bend 0. 00 0. 09 2. 15 -1. 05 4. 68 Stretch-Bend Easier Torsion (or harder? ) Non-1, 4 VDW to 1, 4 bend VDWa -0. 000 2. 12 -0. 55 6. 32 bond 7. 89 6. 56 stretched TOTAL

6 gauche butanes 6 0. 9 = 5. 4 (mnemonic) “Ideal” Minimized Stretches and flattens slightly to reduce VDW Relaxation of Cyclohexane (by Molecular Mechanics) 0. 33 Stretch 0. 00 0. 36 Bend 0. 00 0. 09 Stretch-Bend -0. 000 2. 15 Torsion 2. 12 -1. 05 Non-1, 4 VDW -0. 55 4. 68 1, 4 VDW 6. 32 6. 56 TOTAL 7. 89

End of Lecture 34 Dec. 2, 2009 Copyright © J. M. Mc. Bride 2009. Some rights reserved. Except for cited third-party materials, and those used by visiting speakers, all content is licensed under a Creative Commons License (Attribution-Non. Commercial-Share. Alike 3. 0). Use of this content constitutes your acceptance of the noted license and the terms and conditions of use. Materials from Wikimedia Commons are denoted by the symbol . Third party materials may be subject to additional intellectual property notices, information, or restrictions. The following attribution may be used when reusing material that is not identified as third-party content: J. M. Mc. Bride, Chem 125. License: Creative Commons BY-NC-SA 3. 0